Objective The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. Methods We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted ? co-efficient. Results Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. Conclusion Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.
Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank / Loganathan, A.; Zanframundo, G.; Yoshida, A.; Faghihi-Kashani, S.; Ventura, I. B.; Dourado, E.; Bozan, F.; Sambataro, G.; Yamano, Y.; Bae, S. S.; Lim, D.; Ceribelli, A.; Isailovic, N.; Selmi, C.; Fertig, N.; Bravi, E.; Kaneko, Y.; Saraiva, A. P.; Jovani, V.; Bachiller-Corral, J.; Cifrian, J.; Mera-Varela, A.; Moghadam-Kia, S.; Wolff, V.; Campagne, J.; Meyer, A.; Giannini, M.; Triantafyllias, K.; Knitza, J.; Gupta, L.; Molad, Y.; Iannone, F.; Cavazzana, I.; Piga, M.; De Luca, G.; Tansley, S.; Bozzalla-Cassione, E.; Bonella, F.; Corte, T. J.; Doyle, T. J.; Fiorentino, D.; Gonzalez-Gay, M. A.; Hudson, M.; Kuwana, M.; Lundberg, I. E.; Mammen, A. L.; Mchugh, N. J.; Miller, F. W.; Montecucco, C.; Oddis, C. V.; Rojas-Serrano, J.; Schmidt, J.; Scire, C. A.; Callaghan, A. S. -O.; Werth, V. P.; Alpini, C.; Bozzini, S.; Cavagna, L.; Aggarwal, R.. - In: CLINICAL AND EXPERIMENTAL RHEUMATOLOGY. - ISSN 0392-856X. - 42:2(2024), pp. 277-287. [10.55563/clinexprheumatol/s14zq8]
Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank
De Luca G.;
2024-01-01
Abstract
Objective The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. Methods We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted ? co-efficient. Results Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. Conclusion Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
